Roche said today that two Phase III trials of bitopertin (RG1678) in adults with persistent, predominant negative symptoms of schizophrenia—such as lack of motivation and social withdrawal—failed to meet their primary endpoints, raising questions about the future of the investigational oral glycine reuptake inhibitor.
In the studies, adding bitopertin to antipsychotic therapy did not significantly reduce the mean change from baseline in the PANSS negative symptoms factor score at 24 weeks compared to placebo, as measured by the positive and negative symptom scale (PANSS). However, bitopertin was generally well tolerated, and its overall safety profile was similar to that seen in a previously reported Phase II trial (NN20372).
Roche did not disclose data from the failed Phase III trials, saying that details will be presented at unspecified “upcoming medical meetings.”
“These results are disappointing for people with negative symptoms because more effective treatments are needed for these debilitating effects of schizophrenia,” Sandra Horning, M.D., CMO and head of global product development at Roche, said in a statement. “We will await data from the remaining bitopertin studies in schizophrenia before deciding on next steps.”
Four additional bitopertin studies remain under the SearchLyte clinical development program, which includes more than 3,600 people across 32 countries: A third Phase III study evaluating bitopertin for persistent, predominant negative symptoms of schizophrenia is ongoing, as are three Phase III studies investigating bitopertin for suboptimally controlled symptoms of schizophrenia.
The latter three studies—TwiLyte (NN25307), MoonLyte (WN25306), and NightLyte (WN25305)—are intended to evaluate the efficacy and safety profile of bitopertin when added to antipsychotic medicines in adults with suboptimally controlled symptoms of schizophrenia: The primary endpoints are the mean change from baseline in the PANSS positive symptoms factor score at 12 weeks.
All six studies are designed to assess bitopertin as a potential add-on or adjunct therapy to antipsychotics for symptoms of schizophrenia not fully addressed by current treatments.
Bitopertin is designed to improve the function of the N-methyl-D-aspartate (NMDA) receptor function, which is thought to be reduced in schizophrenia, by increasing the availability of glycine for receptor activation. Reduced NMDA receptor function is thought to contribute to all core symptom types of schizophrenia.
Bitopertin could have generated up to CHR 2 billion ($2.19 billion) in annual sales upon approval, Andrew Weiss, an analyst for Bank Vontobel in Zurich, told Bloomberg News.